Recombinant DNA Advisory Committee - 06/7-8/93 
hematological protection. 
Review-Dr. Dronamraju 
Dr. Dronamraju stated that Dr. Deisseroth had responded to his earlier concerns about 
the use of primate models. Dr. Deisseroth noted the RAC stated previously that either a 
large animal model or long-term bone marrow cultures were acceptable models, and that 
MDR-1 expression was demonstrated in bone marrow cells after 35 days in Dexter 
culture. 
Review-Mr. Capron 
Mr. Capron raised concerns about the Informed Consent document. Sections 3 and 4 of 
this document which describe the research plan and potential risks and benefits, are 
poorly written and very confusing. The description is too technical (e.g., using terms 
such as "pumping mechanism") rather than using simplified language (e.g., "a gene for 
drug resistance") to refer to the MDR-1 gene. The videotape prepared by the hospital is 
equally confusing. 
Other Comments 
Ms. Meyers said that the Informed Consent document may leave patients with the 
impression that the experimental treatment will cure their cancer. More conditionality 
should be incorporated into the document. She asked whether Dr. Deisseroth has 
obtained enough data from his previously approved protocols to justify approval of an 
additional protocol? 
Dr. Leventhal responded that Dr. Deisseroth's two previously approved protocols are for 
chronic myelogenous leukemia, and that their progress is satisfactory. This protocol is 
for the treatment of ovarian cancer and is a well designed study. 
Dr. Parkman questioned whether the administration of growth factor during 
hematopoietic recovery may obscure the clinical outcome of MDR-1 gene protection of 
Taxol toxicity to bone marrow cells. MDR gene expression will be monitored by 
polymerase chain reaction (PCR) analysis of colonies derived from peripheral blood and 
bone marrow cells following Taxol treatment. An increase in the number of MDR-1( + ) 
colonies following Taxol administration will be a definitive endpoint, even if any 
protective effects due to MDR-1 expression are normalized by hematopoietic cell growth 
factor administration. Furthermore, if MDR-1 transduction does not result in clinical 
benefit because of Taxol toxicity to cells other than the bone marrow cells, the proposed 
study will still provide useful information for future attempts to convey drug resistance to 
hematopoietic cells using other genes which may have greater therapeutic margins. 
Recombinant DNA Research, Volume 17 
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